title: [Hyperfractionated radiotherapy and adjuvant chemotherapy in patients with malignant gliomas].
abstract: BACKGROUND
  Malignant gliomas are the most common primary brain tumours in adults. Postoperative radiation therapy significantly improves survival when compared to surgery alone. It is occasionally followed by the adjuvant chemotherapy (CHT). Since this approach carries a significant hazard of local recurrence, new approaches have been tested in order to improve survival figures, hyperfractionated radiation therapy (HFX RT) and recent multiagent CHT.
  
  
  METHODS
  Fourty eight adult patients with malignant glioma were treated with HFX RT to a total TD of 72 Gy in 60 fractions in 30 treatment days, 1.2 Gy b.i.d. fractions with an interfraction interval of 4.5-6.0 hr. Four weeks after HFX RT, CHT was introduced consisting of BCNU, Vincristine, Procarbazine, and Cisplatin. Six cycles were planned to be administered but CHT was stopped because of tumour progression. Toxicity criteria were made on the basis of joint RTOG/EORTC toxicity criteria.
  
  
  RESULTS
  Median survival time in all 48 patients was 52 weeks, and 1-3 year survival time was 48%, 29%, and 29%, respectively. Median progression-free survival was 30.5 weeks. Patients with AA achieved better results than those with GBM, regarding the overall survival and progression-free survival (p = 0.0000). The univariate analysis revealed that the age, performance status, and extent of surgery were important prognostic factors influencing the overall survival and progression-free survival, as well as tumour location and interfraction interval. The multivariate analysis revealed that the performance status, tumour location, and interfraction interval were independent prognostic factors in patients with GBM. Toxicity of this treatment approach was generally considered as mild, with no late toxicity attributed to HFX RT. CHT-related toxicity was mostly haematological.
  
  
  CONCLUSIONS
  The results of this study are in agreement with those using standard and various altered fractionated regimens in malignant glioma. They add evidence that this combined approach is feasible and well tolerated by the patients. Although there is some controversy about dose-escalation in HFX studies in the past, the studies reporting no significant improvement in survival for HFX RT were probably due to somewhat lower total doses used in them. Since this approach contributed to a 3-year survival of 83%, and 3-year progression-free survival of 70% in AA patients (all treated with 4.5 hr interfraction interval), they could serve as a basis for further studies measuring late effects as an endpoint, since there are data showing that aggressive treatment might be hazardous in patients with AA.
authors.affiliation: Department of Oncology, Clinical-Hospital Centre, Kragujevac.
authors.forename: V
authors.initials: V
authors.lastname: Jeremić
authors.forename: D
authors.initials: D
authors.lastname: Grujicić
authors.forename: M
authors.initials: M
authors.lastname: Samarcić
authors.forename: V
authors.initials: V
authors.lastname: Antunović
authors.forename: M
authors.initials: M
authors.lastname: Joksimović
authors.forename: B
authors.initials: B
authors.lastname: Milicić
authors.forename: L
authors.initials: L
authors.lastname: Rasulić
authors.forename: N
authors.initials: N
authors.lastname: Nikolić
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D019583:Dose Fractionation, Radiation; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D015996:Survival Rate
vernacular_title: Hiperfrakcionisana radioterapija i adjuvantna hemioterapija kod bolesnika s malignim gliomom.